Compositions for transfecting resistant cell types

Abstract

A transfection reagent composition comprising: 30-60 MOL. % of a cationic lipid, or a pharmaceutical acceptable salt thereof; 10-60 MOL % of a structural lipid; 10-20 MOL % of a triglyceride; and 0.1 to about 10 MOL. % of a stabilizing agent, is provided. The transfection agent is effective in transfecting cells, particularly neurons, with siRNA, mRNA and plasmid nucleic acid, Sand maintaining viability of the cells as well as activity of the delivered nucleic acid.

What is claimed: 
     
       1. A composition for transfecting nucleic acid into live cells comprising:
 (a) 40 mol % of a cationic lipid comprising 1,17-bis(2-octylcyclopropyl)heptadecan-9-yl-4-(dimethylamino) butanoate or a pharmaceutically acceptable salt thereof; 
 (b) 20-40 mol % of a structural lipid, wherein the structural lipid is DOPE; 
 (c) 10-20 mol % of a triglyceride, wherein the triglyceride is triolein; and 
 (d) about 2.5 mol % of a stabilizing agent, wherein the stabilizing agent is polyoxyethylene (40) stearate. 
 
     
     
       2. The composition of  claim 1 , further comprising a sterol. 
     
     
       3. The composition of  claim 2  wherein the sterol is cholesterol. 
     
     
       4. The composition of  claim 1 , further comprising a nucleic acid. 
     
     
       5. The composition of  claim 4 , wherein the nucleic acid is DNA, RNA, a locked nucleic acid, a nucleic acid analog, or a plasmid. 
     
     
       6. The composition of  claim 4  wherein the nucleic acid is single or double stranded. 
     
     
       7. The composition of  claim 4 , wherein the composition exists in the form of nanoparticles having a diameter of from about 15 nm to about 300 nm. 
     
     
       8. A method for introducing a nucleic acid into a cell, for modulating the expression of a target polynucleotide or polypeptide in said cell while maintaining activity of the nucleic acid and viability of the cell, comprising contacting the cell with the composition of  claim 4 . 
     
     
       9. The method of  claim 8 , wherein the cell is a neuron or an astrocyte. 
     
     
       10. The method of  claim 8  wherein the cell is a mammalian cell. 
     
     
       11. The method of  claim 8 , wherein the contacting occurs in vitro. 
     
     
       12. The method of  claim 8 , wherein the contacting occurs in vivo.